A recent FDA approval of a label expansion put the three marketed therapies for spinal muscular atrophy (SMA) on equal footing for the youngest patients. And recent survey found that many payers are covering sequential use of the costly agents, including a gene therapy.
The FDA initially approved Evrysdi (risdiplam) from Roche Group member Genentech USA, Inc. on Aug. 7, 2020, for the treatment of SMA in people at least 2 months old. On May 30, 2022, the agency expanded the drug’s label to include the treatment of infants less than 2 months old. The survival motor neuron 2 (SMN2) splicing modifier is an oral solution administered by mouth or feeding tube and can be administered by a patient or caregiver at home after a recommended consultation with a health care professional prior to the first dose.
That label expansion meant that Evrysdi joined two other therapies in being indicated for infants with the most severe type of SMA. The first SMA drug on the market was Biogen’s Spinraza (nusinersen), which the FDA approved on Dec. 23, 2016, for the treatment of SMA in pediatric and adult patients. The SMN2-directed antisense oligonucleotide is administered by or under the direction of health care professionals over one to three minutes as an intrathecal injection. That drug was followed by the May 24, 2019, approval of Novartis Pharmaceuticals Corp. subsidiary AveXis, Inc.’s Zolgensma (onasemnogene abeparvovec-xioi) for the treatment of patients less than 2 years old with SMA with bi-allelic mutations in the SMN1 gene. Dosing for the gene therapy is a one-time 60-minute intravenous infusion.
People with SMA cannot produce enough SMN protein, leading to the loss of motor neurons, which results in problems breathing, swallowing, speaking and walking. Before a therapy was available to treat SMA, the condition was the No. 1 genetic cause of infant death.
Most physicians recognize four types of SMA:
- SMA Type 1: This is also known as Werdnig-Hoffmann disease and can impact infants in utero in the most severe form, known as Type 0, which some people recognize as a fifth type. It usually is evident before the child is 6 months old. Most children with Type 1 will die before they are 2 years old if untreated.
- SMA Type 2: Also known as Dubowitz disease, this form produces symptoms in children between 6 and 18 months of age. Most patients live into adolescence or young adulthood.
- SMA Type 3: This also is known as Kugelberg-Welander disease. Symptoms present after 18 months of age. With treatment, most patients live a normal lifespan.
- SMA Type 4: People with this form can develop symptoms as early as 18 years old and usually after they are 30 years old; their life expectancy is not affected.
Treatment Is Costly
The condition is not inexpensive to treat. The first-year price of Spinraza is $765,000 and then $382,500 for subsequent years. The price of Evrysdi is tied to a person’s weight and is capped at $340,000 per year once someone reaches 44 pounds. For a 15-pound patient, the price would be less than $100,000 per year. And Zolgensma’s price is $2.125 million.
For the Managed Care Biologics and Injectables Index: Q1 2022, between March 3, 2022, and April 7, 2022 — before Evrysdi’s label expansion — Zitter Insights polled 25 neurologists. Eighty percent had prescribed Spinraza over the 12 months prior to the survey, 68% had prescribed Evrysdi, and 44% had written a script for Zolgensma.
Zitter Insights and AIS Health are both MMIT companies.
During the same time frame, Zitter Insights also polled 36 commercial payers with 117.1 million covered lives and 26 Medicare payers with 38.6 million lives. Respondents covering 92% of commercial lives said that they do not allow the use of more than one SMA therapy at the same time.
“Currently, there are no published clinical trials that demonstrate the effectiveness of combination therapy, so this survey result is not surprising,” says Dea Belazi, Pharm.D., M.P.H., president and CEO of AscellaHealth. “Each of the approved therapies currently has ongoing clinical trials that are addressing effectiveness after other prior SMA treatments and other SMA patient populations but not combination therapy trials. Since Evrysdi and Spinraza have similar mechanisms of action, there currently does not appear to be a documented clinical rationale supporting concurrent therapies.”
The survey also found that payers with 82% of lives said they allow sequential use of the agents.
“There are no published studies demonstrating additional benefit of sequential therapies,” Belazi notes. However, the results of the ongoing trials of sequential use of the treatment “will provide significant insight and clarity into the application of subsequent treatments and the proper sequencing of the available SMA therapies, as well as the best patient candidates for potential subsequent treatments.”
“The new expanded indication now places Evrysdi on even indications with Zolgensma with respect to starting age,” points out Winston Wong, Pharm.D., president of W-Squared Group. “Evrysdi can be seen as an oral form of Spinraza, impacting the SMN2 gene; is less expensive than Spinraza; and potentially more effective than Spinraza with its more systemic clinical effect as opposed to Spinraza being an intrathecal injection and limiting its site of action to the CNS [i.e., central nervous system]. As a result, Evrysdi appears to also impact other genes as well.
“The real question still is for the type 1 and 2 SMA patients and the question of Zolgensma vs. Evrysdi,” he continues. “Zolgensma is replacing the more potent SMN1 type gene, whereas Evrysdi impacts the SMN2 gene, which produces a lower amount of functional SMN proteins. In my mind, the market will continue to sequence between Zolgensma and Evrysdi. I do not need see a niche for Spinraza.…Due to Zolgensma correcting the SMN1 gene, over Evrysdi’s SMN2 gene, I see Zolgensma being used first and then sequencing over to Evrysdi” except in situations where “Zolgensma is not indicated due to the mutation not meeting the indication criteria.”
Evrysdi’s broadened indication “expands the opportunity to begin treatment at home rather than having to have to use the intrathecal (Spinraza) or the infusion (Zolgensma) routes of administration,” observes Belazi.
“Payers will typically restrict these therapies through prior authorization using the criteria from the pivotal clinical trials, which is typically more restrictive than the FDA-labeled indication,” he explains. With the new approval, “payers may need to review current coverage policies to address both the current age requirement, as well symptomology and symptom severity criteria.”
The Institute for Clinical and Economic Review (ICER) published an Effectiveness and Value report in 2019 on Spinraza and Zolgensma in SMA that was updated the same year. Belazi points out that ICER determined that neither agent met “the traditional cost-effectiveness thresholds in any population of use, and in order to meet these thresholds, the product pricing would need to be substantially reduced. Evrysdi was not included in this report, but it is reasonable to assume that given the pivotal clinical trial patient population, results and product pricing, a similar conclusion would be likely. With the addition of efficacy demonstrated in pre-symptomatic patients, there will be a challenge to demonstrate long-term cost-effectiveness under the ICER guidelines for this patient population.”
For more information on the Zitter Insights data, contact Jill Brown Kettler at firstname.lastname@example.org.
Contact Belazi through Caroline Chambers at email@example.com and Wong at firstname.lastname@example.org.
By Angela Maas